Project Summary Tobacco use is the leading cause of cancer and the leading preventable cause of death. Alcohol use is responsible for ~88,000 deaths each year in the U.S. and is another primary preventable cause of cancer. The changing cannabis policies and the 8% increase in cannabis use in the last decade have brought new challenges for existing treatment efforts. Our recent studies among TTU college students indicate that over 50% of those who reported alcohol intoxication, tobacco use, or cannabis use in the past month were involved in two or more of these substances (alcohol, tobacco and cannabis - ATC). Growing evidence has shown that polysubstance use is associated with numerous and deleterious consequences for college-attending emerging adults, but they are often unmotivated to quit or reduce drug use. Therefore, there is an urgent need to address this critical public health issue of widespread polysubstance use in high risk college students. Despite multiple treatment efforts, outcomes are far from optimal since treatments often fail to capitalize on important target domains linked to addiction outcomes. Research shows that one target domain (mechanism) for ATC involves deficits in self-control networks including the prefrontal cortex (PFC), the anterior cingulate cortex (ACC), and the ACC-Striatum circuit. Based on previous research conducted by our team and others, self-control deficits have been linked to SUDs, and could be ameliorated through mindfulness meditation (MM) and/or EEG neurofeedback (NF), both of which target self-control networks and have the potential to minimize negative outcomes resulting from deficits in self-control. Although MM has shown promises in improving self- control and reducing ATC use, many struggle to engage in the mindfulness practice early in treatment. Promisingly, recent studies suggest that combining NF with MM may improve engagement with mindfulness practice and produce larger reductions in ATC use compared to MM alone. The goal of this project is to understand brain mechanisms of ATC reduction following brief IBMT, and optimize IBMT through EEG Neurofeedback (NF). We will assess self-control deficits and ATC use and examine the effects of IBMT and/or NF on improving self-control and reducing ATC use among TTU college students. Our study will be the first to reveal the brain mechanisms of combining mindfulness intervention and EEG neurofeedback for treating polysubstance use, and potentially provide preliminary evidence that the modulated self-control networks by IBMT+NF are associated with clinical benefits such as craving and ATC reduction in high risk college students.